Cardiac hypertrophy (CH) is a major risk factor of cardiovascular mortality and morbidity. It is induced by hemodynamic overload, as well as by neurohumoral factors. The signals which mediate the increased physical pressure into the hypertrophic response have not been elucidated. In the present study, we try to identify stimuli which participate in the hypertrophic response, and determine the stage of CH in which they play a role. For this purpose, CH is induced in rats by pharmacological and surgical means. The hearts are excised and examined at different stages after the intervention for their weight, macroscopic and microscopic structure, and molecular markers of CH. An attempt is made to identify specific genes the expression of which differentiate the hypertrophic heart from its normal counterpart, such as growth factors, their receptors, and cell-cycle specific genes. This is carried out by means of Northern blotting and RNAse protection assay for known candidate genes, and by subtractive hybridization in the search for new candidate genes. We found that two distinct patterns of CH are induced by different hormonal stimuli: The first, initiated by excessive exposure to a beta adrenergic agonist, is characterized by rapid onset, large maximal response, reversibility, dependence of the response on angiotensin II levels, and dependence of the extent of the response on age. The second, induced by exposure to an alpha adrenergic stimulus, is characterized by a slow onset, small maximal response, irreversibility of CH in response to cessation of the stimulus, and independence of the response from angiotensin II levels and from age. We are now examining whether the two patterns differ in morphological and molecular aspects. CH characteristic of hypertension seems to show a combination of both patterns. This finding may be helpful in the design of treatment for hypertension and other cardiovascular conditions associated with cardiac hypertrophy.